Abstract
In order to establish a genotype-phenotype relationship, we have identified both mutant phenylalanine hydroxylase (PAH) genes in 108 phenylketonuria (PKU) patients (27 different alleles, 54 different genotypes). One major group of patients with very high pretreatment phenylalanine values (“classical” PKU) exclusively comprised homozygotes of the PKU mutations I65T, G272X, F299C, Y356X, R408W, IVS12nt1, and compound heterozygotes of various combinations of these alleles with G46S, R261Q, R252W, A259T, R158Q, D143G, R243X, E280 K, or Y204C. A second major group of patients with lower phenylalanine values (“mild” PKU) comprised mutations A300S, R408Q, Y414C in various compound heterozygous states, and R261Q, R408Q, Y414C in homozygotes. The phenylalanine values in these groups were non-overlapping. In addition, a smaller group of patients formed the transition between the two main groups. In sib pairs 4 of 15 had discordant pretreatment phenylalanine values.
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Abbreviations
- PAH :
-
phenylalanine hydroxylase
- PKU :
-
phenylketonuria
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Eiken, H.G., Knappskog, P.M., Motzfeldt, K. et al. Phenylketonuria genotypes correlated to metabolic phenotype groups in Norway. Eur J Pediatr 155, 554–560 (1996). https://doi.org/10.1007/BF01957904
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DOI: https://doi.org/10.1007/BF01957904